Thienylquinolin carboxylic acids



UNITED STATES PATENT OFFICE.

MAX HAR'IMANN AND ERNST WYBERT, 0F BASED, SWITZERLAND, AS$IGNOR$ '10 SOCIETY OF CHEMICAL INDUSTRY IN BASIJE, OF BASEL, SWITZERLAND.

THIENYLQUINOLIN CARIBOXYLIG AGIDS.

Ito Drawing. Application filed October 2 new and useful Thienylquinolin-Carboxyhc Acids, of which the following is a clear, full, and exact specification.

We have found that the acetothienone which can be obtained from thiophene and acetylchlorid according to the reaction of condensed under the action of convenient condensing agents with isatin to Q-thienylquinolin-t-carboxylic acid. In the same way other isatin compounds, as for instance, derivatives and products of substitution of isatin can be condensed with acetothienone to correspondingly substituted thienylquinolirhcarboxylic acids. 'As condensing agents, there can be employed for example alcoholic or aqueous alkalis or earth-alkalis.

' selves can be converted, according to known methods, into their desired derivatives, as

for instance salts, esters, amids, etc.

The 2-thienylquinolin-4-carboxylic acid corresponds to the following formula:

COOP;

It resembles consequently .with respect to its constitution Z-phenylquinolin 4 carboxylic acid, the well known antiarthritic substance. The entrance of the thiopheneradical in lieu of the phenyl-group causes, however, an important change of the physiological effect. The most striking property is an extraordinarily pronounced formation of coloring matter in the'body. If, by way of experiment, only small quantities of the non poison'ous -2-thienylquinolinl-carboxylic .acid are administered to an animal, there occurs immediately an intensive violet coloration extended on all parts of the animal body. Besides the urine shows the color of? concentrated solution. of potassium permanganate. On dissecting it is found that the nerves remain entirely free from the coloration. The coloring matter which can be eliminated from the urine in form of intensively violet colored crystals The obtained acids them-- during 3 hours, on the water bath.

. cultly soluble in water,

crystallized from hot water.

Specification of Letters Patent. Patented Aug. 24, 1920.

1, 1918. Serial No. 258,957.

dissolves diflicultly in water and dilute acid, easily in alkalis forming deeply colored alkali salt-s, somewhat easily in cold alcohol and diflicultly in ether, while it is insoluble in. benzene and toluene.

The 2-thienylquinolin-4-carboxylic acids and their derivatives serve for histological and therapeutical purposes. The 2-thienylquinolin-4r-carboxylic acid is. particularly employed for vital coloration. It possesses the property of selective coloration of the tissues. It colors intensely for instance the fascioe, the sinews, the tendons and the cartilages, but does not color the skeleton muscles, the interior of the-milt, the pancreas, the supra-renal gland, the brain and the nerves. It colors the tissues of the human body as intensively as those of the animal I body. A single administration of about 0.5

\ Ema ample 1.

80 gr. of Q-acetothiehone, 88 gr. of isatin, 470 c. c. of potash-lye 0t 28 per cent. and 7 O c. c. of .alcohol are cooling, the Q-thienylquinolinl-carboxylic acid is precipated by acetic acid and recrystallized from alcohol. It forms small yellow leaves of the fusion point 211. It is diilidissolves' somewhat easily in hot alcohol; it is soluble in sodium carbonate and soda-lye. It can be precipitated from alkaline solutions by means of diluteacids. It is also soluble in an excess of strong acids.

Eoample Q.

22 partsof acetothienone are dissolved in 20 parts of alcohol and the resulting solution is heated to boiling in an apparatus provided with a reflux condenser, 'for3 hours, with 6, parts of sodium dibromisatinate and 120 parts of soda lye of 28 per cent. fter cooling, the sodium salt' of the 2-thienyl1 6.8-dibromquinolini-carboxylic acid sep aratesin large bright leaves which are reviolet coloration re- From the so-- heated, while stirring, After i acid by acetic acid or a dilute mineral acid. It crystallizes from alcohol or glacial acetic acid.

What we claimis: '1. As new products the herein described 1 Q-thienylquinolin 4 carboxylic acids, ch-

tained by condensing isatin compounds with acetothienone, which constitute well crystallized compounds of'determined fusion point, are easily soluble in most of the organic solvents and in strong mineral acids and serve for histological and therapeutical purposes.

2. As a new article of manufacture, the 2-thienylquinolin-t-carboxylic acid derived a from isatin and acetothienone, which crystallizes in form of small yellow leaves of the fusion point 211; dissolves difiicultly in Water, somewhat easily in hot alcohol, is

soluble in sodium carbonate and soda lye ai well as man excess of strong acids, is precipitated from its alkaline solutions by dilute acids and produces, when injected into the animal body, a violet coloring matter which dissloves diflicultly in water and dilute acid, easily in alkalis, somewhat easily in cold alcohol, difiicultly in ether, but is insoluble in benzene and toluene.

In witness whereof we have hereunto signed our names this 9th 1918, in the presence of two subscribing Witmesses MAX HARTMANN. ERNST WYBERT. Witnesses:

H. H. WERTH, AMAND Rrr'rnn.

day of September; 

